Assessing Potentially Inappropriate Prescribing in the Elderly Veterans Affairs Population Using the HEDIS 2006 Quality Measure

BACKGROUND: Studies have found that 20% to 25% of older patients receive drugs identified as inappropriate by the 1997 Beers criteria. After the addition of 22 new drugs to the 2003 Beers criteria, the National Committee on Quality Assurance convened an expert consensus panel to identify which drugs from the 2003 Beers criteria should always be avoided in the elderly. The resulting list of drugs to avoid was added to the 2006 Health Plan Employer Data and Information Set (HEDIS) to measure the quality of prescribing for the elderly. OBJECTIVES: To use HEDIS 2006 criteria to determine the rate of potentially inappropriate prescribing in the elderly (PIPE) and to determine if patient risk factors are similar to those found using Beers criteria. METHODS: This cross-sectional database study identified older patients receiving drugs included in the HEDIS 2006 criteria using national data from the Veterans Health Administration. Patients aged 65 years or older on October 1, 1999, with at least 2 outpatient visit days during fiscal year 2000, ending September 30, or outpatient visits in fiscal years 1999 and 2000 were included (N=1,096,361). Multivariable logistic regression analyses stratified by gender identified patient characteristics associated with increased risk of HEDIS 2006 drug exposure. Since oral estrogens were considered appropriate at the time of this study, they were excluded from the list of HEDIS 2006 drugs. RESULTS: Overall, 19.6% of older veterans were exposed to HEDIS 2006 drugs 23.3% of older veteran women and 19.2% of older veteran men. The most commonly prescribed HEDIS 2006 drugs were antihistamines (received by 9.0% of men and 10.7% of women), opioid analgesics (received by 4.6% of men and 5.8% of women), and skeletal muscle relaxants (received by 4.3% of men and 5.3% of women). Propoxyphene was the most commonly used HEDIS 2006 drug, received by 4.5% of men and 5.7% of women, followed by diphenhydramine, received by 3.5% of men and 4.7% of women, and hydroxyzine, received by 3.2% of both men and women. Patients receiving 10 or more medications of any type were at greatest risk of exposure. Men were 8.2 times more likely to receive at least 1 HEDIS 2006 drug than those taking 1 to 3 drugs of any type (95% confidence interval [CI], 8.0-8.4), while women were 9.6 times more likely (95% CI, 8.2-11.2). CONCLUSIONS: Even though we included a slightly different list of drugs to avoid, results for the HEDIS 2006 measure were similar to those of the 1997 Beers criteria. The HEDIS 2006 drugs are commonly prescribed, and there is a distinct need for direct evidence linking HEDIS 2006 PIPE exposure to adverse patient outcomes. To reduce PIPE, it seems necessary to provide additional evidence for clinicians through the conducting of a well-designed study to assess patient outcomes associated with PIPE exposure as defined by the HEDIS criteria.

The Beers criteria, which are the foundation of this measure, have been controversial since their original publication in 1991 (Table 1). 3,12,14 Because they were derived from expert consensus, some argue that they are not strictly evidencebased. 15 Clinicians contend that these criteria are too broad because some Beers-criteria drugs may be appropriate for specific patients in certain circumstances. Moreover, findings from extant outcomes studies have not consistently linked PIPE, as defined by a dichotomous measure based on the Beers criteria, to negative patient outcomes. 6,8,[16][17][18][19] The fact that only small changes in prescribing patterns have occurred over time in the most commonly used PIPE drugs (e.g., propoxyphene) 20,21 may indicate inadequate training of physicians in the principles of geriatric practice. 22 Alternatively, it may mean that clinicians put little stock in the Beers criteria. Although the HEDIS 2006 criteria are derived from the drugs thought to be the most problematic, many clinicians may believe that there is insufficient evidence for harm from some of these agents. The stability of the volume of propoxyphene use in older patients suggests that modification of prescribing patterns may be a significant challenge.
Since the quality of prescribing for older patients is now being judged using this quality measure, it is important for managed care plans to understand the magnitude of PIPE exposure and to identify patients most at risk based on these new criteria. This will enable the managed care plans to successfully develop and implement interventions designed to improve prescriptions for older Americans. Because 14 of the drugs included in the HEDIS 2006 criteria ( Table 2) were recently added, estimates of PIPE exposure based on these criteria have not yet been published. Accordingly, the objective of this study is to determine if the prevalence and predictors of inappropriate drug use as defined by HEDIS are similar to those for the 1997 Beers criteria 3 for which more information is known. Since oral estrogens were recommended for use in certain women at the time of this study (2000) and prescribing patterns have likely changed since the publication of the Women' s Health Initiative Study findings in 2002, our analysis excludes assessment of estrogens. Because a number of commonly used drugs (e.g., amitriptyline, oxybutynin) were excluded from the HEDIS 2006 criteria, we hypothesized that rates of PIPE using these criteria will be lower than rates reported in studies using the Beers criteria.
ss Methods

Data Sources and Population
This retrospective cross-sectional study was conducted using administrative data from the National Patient Care Database (NPCD) linked to outpatient pharmacy data for fiscal year (FY) 2000 (i.e., October 1, 1999, through September 30, 2000. The Department of Veterans Affairs (VA) utilizes an all-electronic medical record-the Veterans Health Information Systems Technology and Architecture-which transmits data each night on all patient care received from each VA facility to the national data repository in Austin, Texas. Thus, all inpatient and outpatient care received in the VA health system is documented. Individuals receiving care are identified using encrypted identifiers that are consistent in all VA databases; this allows the linking of individual data components to create a complete administrative record of the care provided to any VA patient. Administrative data include demographic and diagnostic information (International Classification of Diseases, Ninth Revision, codes) 23

Identification of Inappropriate Prescribing
Initially, patients who received any HEDIS criteria drugs were identified. In general, VA administrative data on race/ethnicity represent a combination of self-report and provider-identified information. Missing race/ ethnicity data were supplemented using self-reported data from the 1999 Large Health Survey of Veterans, a nationally representative survey of VA enrollees (July 1, 1999, through January 1, 2000); these self-reported data have been found to be consistent with VA administrative data. 26,27 The VA Office of Quality and Performance (guardians of the Large Health Survey) also uses the same encrypted identifiers found in other VA databases, allowing accurate linking to administrative data.

Assessing Potentially Inappropriate Prescribing in the Elderly Veterans Affairs Population Using the HEDIS 2006 Quality Measure
Disease burden. Using a method adapted from Schneeweiss et al., we used a count of comorbidities and a count of unique medications to assess disease burden. 28 For the comorbidity count, we used Selim' s physical and mental health comorbidity indices (CIs) developed for the veteran population to assess comorbid conditions. 29 We chose Selim' s CIs rather than the Deyo version of the Charlson Comorbidity Index since the Charlson index was developed to predict mortality, and our purpose was to assess a broader measure of disease burden that may be associated with functional limitations. The physical CI consists of a count of 26 chronic physical diseases, and the psychiatric CI includes 6 mental health conditions. Scores on each CI are associated with health status: high counts of comorbidities are associated with lower scores (lower health status) on all SF-36 scales. 30 Moreover, higher counts of comorbidities on each CI are significant predictors of outpatient utilization and mortality. [29][30][31] Because our earlier study published in 2005 identified any mental health condition as increasing the risk for PIPE as defined by the Zhan criteria 24 and new drugs added to the HEDIS PIPE criteria are for treatment of psychosis, we categorized the type of psychiatric comorbidity as being either serious mental illness (SMI; psychoses, including bipolar disorder) 32 or other mental illness. To accommodate those with both SMI and other mental illness, we developed 4 categories: (a) no psychiatric diagnosis, (b) SMI (schizophrenia, bipolar disorder), (c) other mental illness (depression, anxiety, posttraumatic stress disorder, substance abuse), or (d) both SMI and other mental health diagnoses. To ensure the complete identification of all relevant diagnoses, we assessed comorbidity status for up to 3 years (FY 1998 through FY 2000).
We identified each drug received by its generic name. We then counted the number of unique oral, topical, and injectable medications received by the patient in FY 2000. Drugs with different doses or formulations were counted as a single medication. Initial bivariate analyses found a correlation between the number of physical diagnoses and the number of unique medications (r = 0.69). Additional analyses further indicated that the number of unique medications was a better predictor of PIPE and that including the number of physical comorbidities did not add significantly to the model. Thus, our multivariable assessment of disease burden for the present study included psychiatric comorbidity and the number of unique medications.
Opportunities for prescription. Finally, we identified the number of outpatient visits each patient received in a clinic where a prescription may be written. Not only does this measure an opportunity for a prescription, it also provides an underlying measure of disease burden since those patients with more comorbid disease generally receive more care.

ss Analysis
The prevalence of PIPE defined by HEDIS was calculated among the entire cohort, while analyses examining patient characteristics associated with use of HEDIS-criteria drugs were conducted only among patients who received at least 1 drug during the year. Multivariable logistic regression analyses were used to identify patient characteristics associated with the increased likelihood of receiving at least 1 HEDIS criteria drug. Because of the small number of women and a number of significant interactions, analyses were stratified by gender. Patient socio-demographic and clinical characteristics described above were included in the model based upon a priori hypotheses, and the Hosmer-Lemeshow and C-statistics were used to assess general model fit. 33 The Hosmer-Lemeshow goodness-of-fit statistic measures the difference between the observed and fitted values. The sample is stratified by deciles based on estimated probabilities; a goodness-of-fit is assessed by computing the Pearson chi-square statistic between the observed and expected frequencies. 34 The C-statistic is a nonparametric measure of the area under the receiver characteristic curve. It is a widely accepted measure of the degree to which the predicted probabilities from a logistic model adequately classify patients with respect to the observed outcome. 35 Model assumptions were also checked by assessing the proportional odds. All analyses were conducted with SAS 8.2 (©1999-2001 SAS Institute, Cary, NC)

Patient Characteristics by Gender
ss Results This cohort of older veterans (N = 1,096,361) was almost entirely male (98%).  Table 4 shows the use of HEDIS drugs by gender. Overall, 19.6% of the overall cohort received at least 1 drug included in the HEDIS 2006 criteria, and 3.9% received 2 or more HEDIS 2006 drugs. Rates of PIPE varied between women and men; 23.3% of women and 19.2% of men received 1 or more HEDIS drugs. Sedating antihistamines, skeletal muscle relaxants, and certain opioid analgesics were the most commonly used PIPE drugs regardless of gender. Table 5 shows results from logistic regression analyses predicting use of HEDIS 2006 drugs. The count of unique drugs was the strongest predictor for both men and women: the risk increased dramatically for those receiving 10 or more drugs. Even after controlling for the number of medications, we found that patients who were older (≥85 years) or black were at lower risk of PIPE, while Hispanics and those with more outpatient clinic visits were at greater risk regardless of gender. Psychiatric comorbidity was a significant predictor for use of HEDIS 2006 drugs for both men and women. However, the effect for SMI alone did not result in a significant increase in risk for women; only diagnosis with other mental illness (e.g., depression, anxiety) alone or in combination with SMI was associated with higher risk of PIPE for women.

ss Discussion
This study demonstrates that when HEDIS 2006 criteria (excluding estrogens) were applied, rates of PIPE (1 in 5) were similar to those reported in previous studies of drug exposure based on 1997 Beers criteria using the same exposure period, the same unit of analysis, and the same measure. 5  Kaufman et al. 37 examined PIPE using a limited number of Zhan-criteria drugs ("always avoid" drugs and selected other drugs based on usage patterns within that health maintenance organization [HMO]). They found lower rates of PIPE-approximately 5% before prescriber intervention and 2% after prescriber intervention-than found in this and other studies. However, their exposure period was quarterly as opposed to yearly, and the drugs included in their study, with the exception of amitriptyline and indomethacin, were rarely used in other studies. 7 Consistent with previous studies, propoxyphene and antihistamine drugs were commonly used, and women and patients with greater disease burden (as measured by a count of medications and psychiatric comorbidities) were at greater risk of PIPE. 5,7,10,38 However, since the 2006 HEDIS criteria do not include amitriptyline, skeletal muscle relaxants replaced psychotropic drugs as the third most commonly used class of drugs. These agents are notorious for their anticholinergic and sedative side effects. Most experts would agree that, for spasms, preferred alternatives (e.g., acetaminophen in combination with a weak opioid such as oxycodone) would provide adequate pain relief. 39 Usage rates of antihistamines, opiate analgesics, and skeletal muscle relaxants were high for both men and women, but rates were higher for women than for men and accounted for much of the gender difference in PIPE exposure. Since antihistamines, skeletal muscle relaxants, opiates (predominantly propoxyphene), and psychotropic medications account for most PIPE exposure, this study suggests that research examining why these drugs continue to be so commonly used may be important to the development of successful interventions to reduce PIPE in both women and men. These drugs are often requested by patients, thus a focus on provider and system factors associated with their use may not be adequate. Further exploration of the patient' s role in this decision-making process is needed.
This study also highlighted an increased risk of PIPE in patients with psychiatric comorbidities. Several prior studies suggested that PIPE is more common in patients with depression. [40][41][42] Our data suggest that diagnoses such as depression and anxiety are associated with PIPE for all patients, but comorbid SMI adds to this risk, particularly for men. Post hoc analyses found that not only are patients with psychiatric comorbidities at greater risk of receiving psychotropic drugs, but they are also at risk of receiving other classes of drugs. In particular, both men and women with all types of psychiatric comorbidities were also more likely to receive inappropriate antihistamines, and men were also more likely to receive inappropriate antibiotics. Antihistamines may be used specifically to counteract pseudo-Parkinsons symptoms associated with the use of older antipsychotic drugs 43 or to treat anxiety or insomnia in patients for whom benzodiazepines may be problematic (e.g., patients with substance abuse disorders). Patients with multiple mental illnesses may require different medications for each condition to adequately control symptoms, and the polypharmacy itself may lead to a prescribing cascade to deal with resultant side effects. 44 Post hoc analyses also indicated that patients with SMI were less likely to receive inappropriate opiate analgesics and skeletal muscle relaxants, while those with mood disorders were more likely. Those with affective disorders may report somatic complaints to a greater degree than those with SMI and thus be more prone to receiving inappropriate drugs to address these complaints. 45 Alternatively, patients with chronic back and other types of pain are at risk for depression, resulting in the relationship between other mental illness and PIPE. 46 These findings suggest that more thorough investigation of the relationship between PIPE and mental illness is needed to better understand this risk, in order to develop ways to improve prescribing to this population.

Logistic Regression Model Predicting HEDIS 2006 Drug Use
Another important contribution of this study is that, consistent with some prior studies, 38,[47][48][49] the oldest of the elderly were at lower risk of PIPE and the youngest of the elderly were at greater risk. This suggests that providers become increasingly cautious as patients age and physical health deteriorates. This finding also suggests that defining "elderly" as 65 years and older may be arbitrary. The age of 65 was identified as retirement age in 1883 by Otto von Bismarck when the average life span was 47 years. 50 This age was adopted as the age of retirement in the United States when the Social Security program was initiated. Since that time, the life span has increased to 74.5 for males and to 79.9 for females. 51 The elderly population is healthier today than ever before, and it is a highly homogeneous population. 52 For instance, in 1994 the percentage of individuals who reported no disability was 89% for ages 65 to 74 years, 73% for ages 75 to 84 years, and 40% for ages 85 years and older. 53,54 Should all drugs from the HEDIS 2006 criteria be avoided by all persons 65 years and older? Should these drugs be restricted to older patients with certain physical conditions or limitations? 55 While these questions have not been adequately examined, the HEDIS criteria are targeted to all patients aged 65 years and older.

Limitations
Our study does have some limitations. First, the medications examined included only those prescribed within the VA health system. This may underestimate exposure, particularly for drugs that can be obtained over the counter (e.g., antihistamines). However, the highest copayment at the time of this study was $2 for a 30-day supply-which is much less than the cost of a 30-day supply of over-the-counter drugs. Since diphenhydramine-which can be obtained over the counterwas the most commonly used antihistamine and antihistamines were the most commonly used group of PIPE drugs, our estimates seem reasonable. Moreover, some VA patients may receive medications through Medicare HMOs. Shen et al. found that 33% of VA patients with Medicare eligibility received care in both systems, 56 and a recent small survey found that 18% of VA patients (not necessarily Medicare-eligible patients) received medications from both VA and private-sector HMOs. 57 As we have no way to identify these patients, the effect on our findings is unknown.
Second, our data included only a small number of women. Since these findings are consistent with findings from other national database analyses of 1997 Beers-criteria drugs and with findings assessing preliminary HEDIS criteria using a sample of 10 managed care organizations, 58 we believe that our findings, which were stratified by gender, may be generalizable. However, further research confirming this finding is warranted.
Third, the data for this study were from services received in 2000-5 years before the final development of the HEDIS 2006 criteria. However, these data provide an accurate picture of the types of patients who received these drugs at that time. More importantly, these data provide a benchmark for assessing change in the prevalence of drug use prior to publication of these criteria. With this data point, assessment of change in practice both before and after publication of the HEDIS 2006 criteria can be more accurately ascertained. However, further evaluation of PIPE exposure for women is needed since we excluded estrogen because results from the Women' s Health Initiative Study were not available at the time these data were obtained. Finally, we restricted this analysis to patients who received at least 2 outpatient visits in the VA health system. This restriction excluded approximately 300,000 patients and may bias the cohort to those with greater disease-burden, but we thought it important to improve our ability to identify comorbid conditions. Analyses using the full cohort found lower rates of PIPE (17.5% vs. 19.6% in the restricted sample), but analyses on the full cohort yielded similar findings.

ss Conclusions
These data suggest that PIPE exposure remains substantial for both men and women. The study produced these findings even though we limited the definition of PIPE to a select group of drugs included in the 2003 Beers criteria. While controversy has surrounded using the Beers criteria to measure PIPE, this HEDIS measure is now used to assess the quality of prescribing for older patients. It is unknown whether this quality measure will stimulate change in prescribing patterns, but implementation of a similar quality measure by the Centers for Medicare and Medicaid Services resulted in only small reductions of PIPE for patients in nursing facilities over a 4-year period, perhaps because of substantial prescribing changes that preceded the study. Nonetheless, Briesacher et al. reported that the changes that did occur in prescribing could not be attributed to implementation of the quality measure. 59 It is likely that a similar situation exists for attempts to change prescribing patterns in community-dwelling elderly. Consequently, it will be important to identify barriers to more appropriate care at all levels, including the patient, provider, and the health care system, before effective interventions to reduce PIPE can be developed and implemented by managed care organizations. 60,61 Furthermore, the findings of Stuart et al. that there was little change in the most commonly used drugs, 20 in conjunction with findings from Briesacher at al., 21 suggest that providers may need additional evidence before they change prescribing patterns. 60,62,63 The inconsistency in findings from studies evaluating outcomes associated with exposure to Beers-criteria drugs based on a dichotomous measure 8,[17][18][19]21 may merely be the result of methodological problems, such as failure to use an incident cohort in analyses or poor ascertainment of the temporal relationship between drug exposure and patient outcome. 64 Thus, an important step in changing prescribing patterns is to provide additional evidence for clinicians by conducting a welldesigned study to assess patient outcomes associated with PIPE exposure as defined by the HEDIS criteria. Still, if findings suggest a lack of association between PIPE exposure and negative patient outcomes or findings suggest that PIPE drugs are particularly problematic for the oldest of the elderly but not for the youngest, they will stir additional debate and perhaps encourage the development of a new measure of PIPE.